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Background: Renal replacement therapy (RRT) plays a crucial role in managing acute pancreatitis (AP). This study aimed to develop and evaluate predictive models for determining the need for RRT among patients with AP in the intensive care unit (ICU). Methods: A retrospective selection of patients with AP was made from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version V2.0). The cohort was randomly divided into a training set (447 patients) and a validation set (150 patients). The least absolute shrinkage and selection operator (LASSO) regression cross-validation method was utilized to identify key features for model construction. Using these features, four machine learning (ML) algorithms were developed. The optimal model was visualized and clarified using SHapley Additive exPlanations (SHAP) and presented as a nomogram. Results: The mean age of the cohort was 59.17 years, with an average Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 17.55. Acute kidney injury (AKI) was observed in 52.43% of patients with AP, and 9.05% required RRT. After feature selection, four of 41 clinical factors were ultimately chosen for use in model construction. The Lasso-Logistic Regression (Lasso-LR) model showed a high discriminative ability to predict RRT risk in patients with AP, with an area under the receiver operating characteristic (AUROC) of 0.955 (95% CI 0.924–0.987) in the training set. In the validation set, it maintained its discriminative performance, achieving an AUROC of 0.985 (95% CI 0.970–1.000). Calibration curves indicated an excellent fit in both sets (Brier scores: 0.039 and 0.032, respectively), suggesting high consistency. Decision curve analysis (DCA) highlighted the Lasso-LR model's significant clinical utility in predicting RRT likelihood in patients with AP. Conclusions: Developed via the LASSO regression cross-validation method, the Lasso-LR model significantly excels in predicting the requirement for RRT in patients with AP, demonstrating its potential for clinical application. [ABSTRACT FROM AUTHOR]

Background and objective: Voluntary blood donations remain a major concern in the Democratic Republic of Congo, increasing morbidity and mortality due to shortages of safe blood. Local studies show low rates of recruitment and retention of voluntary donations, as well as a high attrition rate of former donors. The psychosocial factors involved in deciding to become and remain a voluntary blood donor in sub-Saharan Africa remain poorly understood. Our study therefore aimed to explore the motivational factors and perceptions involved in voluntary blood donation in South Kivu. Materials and methods: We conducted 20 individual interviews, and three focus group discussions were conducted with a total of 26 volunteer donors. As a way of triangulation, two additional focus-groups were held with 19 non-donors. The individual interviews were analysed thematically, using a starting list of 3 predefined units of analysis, namely: initiation, maintenance, and cessation of voluntary blood donation. The data was analysed inductively within these predefined units of analysis to generate possible factors of motivation that were then presented and further discussed during the focus-groups discussions with donors and non-donors. Results: Fear presented as a factor influencing the decisions to donate blood either positively or negatively, from recruitment to maintenance to cessation of donation. Other motivational factors were found to be linked to the perceived meaning of voluntary donation, such as the meaning given to the blood voluntary donation and material or non-material expectations. Our results suggest that expectations for material rewards are still high in the context of poverty. Conclusion: In conclusion, many motivational factors may act as incentives or barriers to voluntary blood donation, including high expectations towards the transfusion system. Local particularities need to be considered when promoting voluntary blood donation. The fear of being abused by the system needs to be addressed, by enhancing accessibility to transfusions. [ABSTRACT FROM AUTHOR]

Throughout the COVID-19 pandemic, underserved populations, such as racial and ethnic minority communities, were disproportionately impacted by illness and death. Ensuring people from diverse backgrounds have the ability to participate in clinical trials is key to advancing health equity. We sought to analyze the spatial variability in locations of COVID-19 trials sites and to test associations with demographic correlates. All available and searchable COVID-19 studies listed on ClinicalTrials.gov until 04/04/2022 and conducted in the United States were extracted at the trial-level, and locations were geocoded using the Microsoft Bing API. Publicly available demographic data were available at the county level for national analysis and the census tract level for local analysis. Independent variables included eight racial and ethnic covariates, both sexes, and twelve age categories, all of which were population-normalized. The county-level, population-normalized count of study site locations, by type, was used as the outcome for national analysis, thereby enabling the determination of demographic associations with geospatial availability to enroll as a participant in a COVID-19 study. Z-scores of the Getis-Ord Gi statistic were used as the outcome for local analysis in order to account for areas close to those with clinical study sites. For both national (p < 0.001) and local analysis (p = 0.006 for Los Angeles, p = 0.030 for New York), areas with greater proportions of men had significantly fewer studies. Sites were more likely to be found in counties with higher proportions of Asian (p < 0.001) and American Indian or Alaska Native residents (p < 0.001). Areas with greater concentrations of Black or African American residents had significantly lower concentrations of observational (p < 0.001) and government-sponsored COVID-19 studies (p = 0.003) in national analysis and significantly fewer concentrations of study sites in both Los Angeles (p < 0.001) and New York (p = 0.007). Though there appear to be a large number of COVID-19 studies that commenced in the US, they are distributed unevenly, both nationally and locally. [ABSTRACT FROM AUTHOR]

Background: The payment methodology for diagnosis-related groups (DRG) has implications for both society and medical institutions. Our study aims to analyse the impact of the reform of the payment policy according to the DRG on the operation of a tertiary hospital in Anhui Province. Methods: Monthly data were collected from April 2020 to September 2023 during the reform period for a tertiary hospital on nine types of operational indicators, including average length of stay (ALOS), number of discharges, number of outpatient visits, percentage of discharged patients undergoing level III or IV surgery, bed turnover rate, inpatient essential drug utilization rate, low-risk group mortality, outpatient subaverage cost and inpatient subaverage cost. The data were divided into two phases according to the time of DRG implementation: pre-reform (April 2020–December 2021) and post-reform (January 2022–September 2023), and the segmented regression model with interrupted time series data was used to analyse the changes in the trend of each type of indicator before and after the reform. Statistical analysis was performed using R software (4.3.1). Results: After the implementation of the DRG, the number of discharges increased by 112 800 patients (95% confidence interval [CI] 31.125–194.484, P = 0.008), the bed turnover rate rose by 1.403% (95% CI 1.028–1.778, P = 0.022) and the percentage of discharged patients undergoing level III or IV surgery decreased by 0.098% (95% CI −0.181 to −0.015, P = 0.022). The low-risk group mortality decreased by 0.016% (95% CI −0.027 to −0.005, P = 0.007), and the inpatient subaverage cost decreased by 81.514 CNY (95% CI −121.782 to −41.245, P < 0.001). However, there were no significant differences in the trends of average length of stay, outpatient visits, inpatient essential drug utilization rate and outpatient subaverage cost after the DRG implementation. Conclusions: The findings show that the DRG reform has positively impacted hospital functioning, including quality, safety, efficiency and costs. Although the average length of stay remained unchanged, there was an increase in discharged patients and outpatient visits, indicating hospitals adapted to the new payment model. The reduction in low-risk group mortality suggests improvements in patient safety and care quality. However, challenges remain, as evidenced by decreased surgical complexity and initial drops in bed turnover rates. While the DRG reform holds promise for enhancing healthcare efficiency and controlling costs, potential negative effects such as patient selection bias and coding changes need to be monitored. Future research should focus on the long-term effects of the DRG policy across different healthcare institutions. [ABSTRACT FROM AUTHOR]

Background: Although the challenges of recruiting to randomised controlled trials (RCTs) are well documented, few studies have focused on the impact that the communication between recruiters and patients has on patients' participation decisions. Recruiters are thought to influence patient decision-making, but the mechanisms by which this occurs are unclear. The aim of this research was to investigate how patients interpret and use the information conveyed to them by healthcare professionals (HCPs) in trial participation decisions. Methods: Three pragmatic UK-based multicentre RCTs were purposively sampled to provide contrasting clinical specialities. Data collection was integrated into each RCT, including audio-recordings of patient recruitment consultations and interviews with patients. Where possible, consultation audio-recordings were linked to interviews to explore how information communicated by recruiters was interpreted and used by patients during their decision-making. Data were analysed thematically, using the constant comparison approach. Results: Twenty audio-recorded recruitment consultations were obtained across the 3 RCTs, combined with 42 interviews with patients who had consented to or declined RCT participation. Consultation and interview data were 'linked' for 17 individual patients. Throughout the patient's clinical pathway, HCPs (both those involved in the RCT and not) influenced patients' perceptions of treatment need and benefit by indicating that they preferred a particular treatment option for the patient as an individual. Whilst patients valued and were influenced by information conveyed by HCPs, they also drew on support from other sources and ultimately framed RCT participation decisions as their own. Patients' willingness to be randomised hinged on perceptions of whether they stood to benefit from a particular treatment and the availability of those treatments outside of the trial. Conclusion: This study supports the need for training and support for healthcare professionals involved throughout the clinical pathway of patients eligible for RCTs, as all healthcare professionals who interact with patients have the potential to influence their perceptions of treatments being compared in the trial. Trial registration: OPTIMA ISRCTN42400492. Prospectively registered on 26 June 2012. Prepare for Kidney Care ISRCTN17133653. Prospectively registered on 31 May 2017. MARS 2 ISRCTN44351742. Retrospectively registered on 5 September 2018. [ABSTRACT FROM AUTHOR]

Background: Intraoperative radiotherapy (IORT) is a convenient treatment techniques for patients with early-stage breast cancer. We aimed to compare the outcome of IORT to that of whole-breast external beam radiotherapy (EBRT) in highly selected breast cancer patients based on the 2023 American Society for Radiation Oncology (ASTRO) Clinical Practice Guideline for Partial Breast Irradiation (PBI). Patients and methods: We reviewed patients who underwent breast-conserving surgery (BCS) and received either IORT or EBRT for early-stage breast cancer between 2014 and 2019. The outcomes of these patients were analyzed and compared across different risk stratifications according to the 2023 ASTRO Clinical Practice Guideline for PBI, which categorized the patients into "recommended", "conditionally recommended", or "conditionally not recommended" groups. Results: A total of 732 patients were enrolled with a mean follow-up time of 5.1 years. Among patients in the recommended group, the locoregional recurrence rates were 2.0% for IORT and 2.3% for EBRT (p = 0.978). Conversely, in the conditionally recommended or conditionally not recommended groups, IORT exhibited significantly higher locoregional recurrence rates compared to EBRT: in the conditionally recommended group, IORT had a recurrence rate of 11.1% versus 3.0% for EBRT (p = 0.044), and in the conditionally not recommended group, IORT had a rate of 13.8% versus 2.5% for EBRT (p = 0.010). Conclusions: The locoregional recurrence rate in the IORT group was comparable to that of the EBRT group for patients recommended for PBI. However, for patients categorized as conditionally recommended or conditionally not recommended for PBI, the IORT group showed a higher locoregional recurrence rate, highlighting the need for careful patient selection. [ABSTRACT FROM AUTHOR]

Post-stroke epilepsy (PSE) is a common complication of stroke, significantly impacting patient's quality of life. Repetitive transcranial magnetic stimulation (rTMS) is an emerging potential non-invasive treatment for PSE. This review explores current evidence for rTMS in PSE, highlighting its potential benefits and limitations. Initial studies suggested that rTMS may reduce the seizure burden. Some studies observed a trend towards fewer seizures within two weeks of treatment initiation, indicating a relatively rapid response. Additionally, rTMS may be more effective when used in combination with medication, particularly for patients with specific lesion locations (frontal/temporal lobes) and seizure types (complex partial seizures). This points towards the potential of personalized treatment protocols. However, current evidence has limitations. Studies often involve small sample sizes and methodological variations, necessitating larger, well-designed trials with standardized protocols to confirm the efficacy and safety of rTMS in PSE. Future research should also focus on the optimization of treatment parameters, including stimulation frequency, duration, coil placement, and treatment course. Long-term studies are needed to evaluate the persistence of treatment effects on seizure control, cognitive function, and overall patient outcomes. Refining patient selection criteria and investigating the underlying mechanisms of therapeutic effects of rTMS in PSE are also crucial areas for future exploration. [ABSTRACT FROM AUTHOR]

Background: Breast thermography originated in the 1950s but was later abandoned due to the contradictory results obtained in the following decades. However, advances in infrared technology and image processing algorithms in the twenty-first century led to a renewed interest in thermography. This work aims to provide an updated and objective picture of the recent scientific evidence on its effectiveness, both as a screening and as a diagnostic tool. Methods: We searched for clinical studies published between 2001 and May 31, 2023, in the databases PubMed and Scopus, that aimed to evaluate the effectiveness of digital, long-wave infrared imaging for detecting breast cancer. Additional documents were retrieved from the studies included in the systematic reviews that resulted from the search and by searching for the names of commercial systems. We limited our selection to studies that reported the sensitivity and specificity of breast thermography (or the data needed to calculate them) using images collected by themselves, with at least five breast cancer cases. Studies that considered breast diseases other than cancer to be positive or that did not use standard tests to set the ground truth diagnosis were excluded, as well as articles written in a language other than English and documents we could not access. We also conducted meta-analyses of proportions of the sensitivity and specificity values reported in the selected studies and a bivariate meta-analysis to account for the correlation between these metrics. Results: Our systematic search resulted in 22 studies, with an average pooled sensitivity and specificity of 88.5% and 71.8%, respectively. However, the differences in patient recruitment, sample size, imaging protocol, equipment, and interpretation criteria yielded a high heterogeneity measure (79.3% and 99.1% I 2 value, respectively). Conclusions: Overall, thermography showed a high sensitivity in the selected studies, whereas specificity started off lower and increased over time. The most recent studies reported a combination of sensitivity and specificity comparable to standard diagnostic tests. Most of the selected studies were small and tend to include only patients with a suspicious mass that requires biopsy. However, larger studies with a wider variety of patient types (asymptomatic, women with dense breasts, etc.) have been published in the latest years. [ABSTRACT FROM AUTHOR]

Background: The clinical management of breast cancer (BC) is mainly based on the assessment of receptor expression by tumour cells. However, there is still an unmet need for novel biomarkers important for prognosis and therapy. The tumour immune microenvironment (TIME) is thought to play a key role in prognosis and therapy selection, therefore this study aimed to describe the TIME in Ethiopian BC patients. Methods: RNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissue from 82 women with BC. Expression of PAM50 and 54 immune genes was analysed using the Nanostring platform and differentially expressed genes (DEGs) were determined using ROSALIND®. The abundance of different cell populations was estimated using Nanostring's cell type profiling module, while tumour infiltrating lymphocytes (TILs) were analysed using haematoxylin and eosin (H&E) staining. In addition, the PIK3CA gene was genotyped for three hotspot mutations using qPCR. Kaplan-Meier survival analysis and log-rank test were performed to compare the prognostic relevance of immune subgroups. Results: Four discrete immune phenotypes (IP1-4) were identified through hierarchical clustering of immune gene expression data. These IPs were characterized by DEGs associated with both immune activation and inhibition as well as variations in the extent of immune infiltration. However, there were no significant differences regarding PIK3CA mutations between the IPs. A downregulation of immune suppressive and activating genes and the lowest number of infiltrating immune cells were found in IP2, which was associated with luminal tumours. In contrast, IP4 displayed an active TME chracterized by an upregulation of cytotoxic genes and the highest density of immune cell infiltrations, independent of the specific intrinsic subtype. IP1 and IP3 exhibited intermediate characteristics. The IPs had a prognostic relevance and patients with an active TME had improved overall survival compared to IPs with a significant downregulation of the majority of immune genes. Conclusion: Immune gene expression profiling identified four distinct immune contextures of the TME with unique gene expression patterns and immune infiltration. The classification into distinct immune subgroups may provide important information regarding prognosis and the selection of patients undergoing conventional treatments or immunotherapies. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is a mosquito-borne virus that causes dengue fever, a significant public health concern in many tropical and subtropical regions. Dengue is endemic in more than 100 countries, primarily in tropical and subtropical regions of the world. Each year, up to 400 million people get infected with dengue. Approximately 100 million people get sick from infection, and 40,000 die from severe dengue. Unfortunately, dengue vaccine development is also marred with various complicating factors, as the forefront candidate vaccine performed unsatisfactorily. Moreover, the only licensed vaccine (Dengvaxia) for children 9 through 16 years of age is available in just a few countries. The treatment difficulties are compounded by the absence of an effective antiviral agent. Exploring plant-based therapeutics for dengue from the laboratory to clinical application involves a multi-stage process, encompassing various scientific disciplines. Individual investigators have screened a wide range of plant extracts or compounds for potential antiviral activity against DENV. In vitro studies help identify candidates that exhibit inhibitory effects on viral replication. Some of the most promising medicinal plants showing in vitro activity against DENV include Andrographis paniculate, Acorus calamus, and Cladogynos orientalis. Further laboratory studies, both in vitro and in animal models (in vivo), elucidate the mechanisms of action by which the identified compounds exert antiviral effects. Medicinal plants such as Carica papaya, Cissampelos pareira, and Ipomea batata exhibited potent platelet-enhancing activities while Azadirachta indica and Curcuma longa showed promising effects in both in vitro and in vivo studies. Based on positive preclinical results, researchers design clinical trials. This involves careful planning of trial phases, patient recruitment criteria, ethical considerations, and endpoints. The most important medicinal plants showing efficacy and safety in clinical trials include Carica papaya and Cissampelos pareira. This review suggests that several promising medicinal plants exist that have the potential to be turned into clinical drugs to treat dengue infection. However, in addition to developing synthetic and plant-based therapies against dengue infection, vector management strategies should be made robust, emphasizing the need to focus on reducing disease incidence. [ABSTRACT FROM AUTHOR]

Objective: With an aging population and higher prevalence of dementia, there is a paucity of data regarding dementia patients undergoing cardiovascular surgery. We examined the nationwide trends and outcomes of cardiovascular surgery patients with dementia to determine its effect on morbidity, mortality, and discharge disposition. Methods: From 2002 to 2014, 11,414 (0.27%) of the 4,201,697 cardiac surgery patients from the Nationwide Inpatient Sample had a preoperative diagnosis of dementia. Propensity-score matching was used to balance dementia and non-dementia groups. Primary outcomes included postoperative morbidity, mortality, and discharge to skilled nursing facility (SNF). Results: Dementia patients were more often male (67%) and 65–84 years old (84%). Postoperative mortality among patients with dementia was lower compared to patients without dementia (3.4% vs. 4.6%, p < 0.05). In dementia patients, there were more complications (65% vs. 60%, p < 0.01), more blood transfusions [OR 1.3, 95%CI (1.1, 1.5), p < 0.01] and delirium [OR 3.6, 95%CI (2.9, 4.5), p < 0.0001). Dementia patients (n = 5,623, 49.8%) were twice as likely to be discharged to SNF [OR 2.1, 95%CI (1.9, 2.4), p < 0.0001]. Dementia patients discharged to SNF more often had delirium (18.2% vs. 12%, p < 0.01), renal complications (17% vs. 8%, p < 0.01), and prolonged mechanical ventilation (15% vs. 8%, p < 0.01). Conclusions: Despite an aging population with increasing prevalence of dementia, patients with dementia can undergo cardiovascular surgery with a lower in-hospital mortality and similar hospitalization costs compared to their non-dementia counterparts. Dementia patients are more likely to experience complications and require discharge to skilled nursing facility. Careful patient selection and targeted physical therapy may help mitigate some dementia associated complications. [ABSTRACT FROM AUTHOR]

Introduction: Rectal prolapse is prevalent in children and the elderly, impacting quality of life significantly. Traditional surgical interventions carry risks, especially in pediatric patients. Ethanol sclerotherapy offers a less invasive alternative, inducing fibrosis and thickening of the rectal wall. Despite its potential benefits, procedural complications are possible, emphasizing the need for careful patient selection and procedural expertise. This study aims to evaluate the safety and efficacy of sclerotherapy in treating rectal prolapse in a tertiary referral center in southern Iran. Methods: Patient records from Nemazee Hospital covering January 2014 to December 2023 were retrospectively analyzed. Pediatric patients undergoing ethanol sclerotherapy for rectal prolapse were included. Data on demographics, presentation, procedures, and outcomes were collected. Ethical approval was obtained, and specific inclusion/exclusion criteria were applied. Statistical analyses were conducted using SPSS version 26. Results: One hundred thirty patients were evaluated, with a mean age of 10.74 ± 5.320 years. Most patients experienced constipation (56.9%). 74.2% responded well to sclerotherapy, with 12.9% needing a second injection. Complications were minimal, with bleeding being the most common (4.6%). Recurrence occurred in 18.6% of cases. Male patients showed a higher total complication rate (P = 0.010). Diarrhea-dominant patients had no recurrences post-sclerotherapy. Age significantly influenced treatment response and recurrence (P = 0.017, P = 0.035). Conclusion: Male predominance contradicted global pediatric rectal prolapse ratios, possibly influenced by cultural factors. Sclerotherapy remains effective, though response rates vary. Older age correlated with lower response rates and higher recurrence. Constipation-dominant prolapse was associated with increased recurrence risk. Male patients had a higher complication rate, highlighting the need for tailored management strategies. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of mental health disorders in the United Kingdom necessitates the exploration of novel treatment modalities. This study aimed to assess the feasibility and acceptability of conducting a randomised controlled trial (RCT) evaluating the efficacy of four osteopathic interventions on psychophysiological and mental health outcomes. Methods: A mixed-methods feasibility study with an explanatory sequential design was implemented. The quantitative phase involved randomising 42 participants into four intervention groups: (1) high-velocity and articulation techniques (HVAT), (2) soft-tissue massage (STM), (3) craniosacral therapy (CST), and (4) a combination approach. Primary outcome measures encompassed recruitment rate, assessment duration, questionnaire completion, intervention attrition, and adverse events. Secondary outcomes included validated assessments of depression, anxiety, stress, psychological flexibility, heart rate variability (HRV), and interoception, administered pre- and post-intervention. Analysis of variance (ANOVA) was employed to evaluate pre-post intervention changes. The qualitative phase comprised semi-structured interviews analysed using thematic analysis. Results: The study achieved a recruitment rate of 21 eligible participants per month, with 54.8% of respondents meeting eligibility criteria. All 33 participants who completed the study underwent interventions and assessments within the allocated one-hour timeframe, with full questionnaire completion. The attrition rate was 21%. No adverse events were reported. Qualitative analysis revealed positive participant experiences, with themes highlighting good practitioner communication, intervention accessibility, and increased bodily awareness. Some participants found the questionnaire battery burdensome. Exploratory quantitative analyses showed variations in effects across interventions for heart rate variability, interoceptive accuracy, and mental health measures, but these results should be interpreted cautiously due to the small sample size. Conclusions: This study provides evidence supporting the feasibility and acceptability of a larger-scale RCT investigating osteopathic interventions for individuals presenting with mild psychological symptoms. The preliminary findings suggest potential efficacy in improving mental health outcomes, warranting further investigation. Trial registration NCT05674071, registered 06/01/2023. [ABSTRACT FROM AUTHOR]

Background: Managing degenerative lumbar diseases is challenging due to the complexity of identifying symptom causes, especially when multiple pathologies coexist. This study evaluated the impact of patient-specific lumbar spine infiltrations on therapeutic strategies in patients with multiple spinal pathologies (MSP) or specific spinal pathologies (SSP). Methods: A retrospective cohort of 176 patients treated for subacute or chronic lumbar pain with targeted spinal infiltrations was analyzed. Patients were categorized based on the presence of MSP or SSP. The primary endpoint was the relief of lumbar spine-specific symptoms following each infiltration. Secondary endpoints included epidemiological factors and comorbidities, while tertiary endpoints focused on post-treatment recommendations and performed treatments. Results: High rates of spinal pain (97.1% in both groups) and radiating symptoms (88.2% in SSP and 92.3% in MSP) were reported. Psychological conditions were significantly more prevalent in female patients (19.4% vs. 7.7%, p = 0.0307), whereas hip osteoarthritis was more common in male patients (20.5% vs. 9.2%, p = 0.0490). Among all infiltration types, lumbar transforaminal injections were the most effective, leading to pain reduction in 80.1% of SSP patients and 72.2% of MSP patients. Facet joint and sacroiliac joint infiltrations also frequently resulted in pain reduction in both groups. Overall, conservative treatment was recommended for most patients (73.3%), while only 22.7% of all evaluated patients were recommended for surgical intervention. Additionally, seven patients received a hip prosthesis. Conclusions: Patient-specific lumbar spine infiltrations effectively relieve pain, support therapeutic decision-making, and tend to favor conservative treatment approaches. These findings highlight the role of infiltration therapies in managing both mixed and specific lumbar spine pathologies, suggesting their potential to reduce the need for surgical interventions. [ABSTRACT FROM AUTHOR]

Background: Chronic diseases are a significant and growing problem of our time. They impair the ability to work and increase the risk of early retirement. To support the return to work, rehabilitation services can be applied for in Germany. Currently, the application system for rehabilitation allows only a limited degree of individualisation of the treatment and is associated with a lack of multidisciplinary communication. To facilitate rehabilitation care planning, we developed a complex intervention. A digital, platform-based case management approach (intervention) will ensure multidisciplinary communication and the tailored selection of medical treatments and/or non-medical support measures. The overall objective is to assess the effectiveness of the intervention compared to treatment as usual (control condition). The German Federal Ministry of Labour and Social Affairs (BMAS) funds the RehaPro-SERVE study (grant number: 661R0053K1). Methods: This is the protocol for an investigator-initiated, pragmatic, multicentre, randomised and controlled two-arm parallel-group superiority trial with embedded qualitative process evaluation. The study will be conducted in Hesse state, Germany. N = 59 primary care physicians will be recruited and tasked with the recruitment of six eligible patients each. Eligibility criteria: age 40–60; minimum of 4-week work disability due to musculoskeletal, oncologic or psychological conditions or the post-COVID-19 syndrome within the last 6 months; at high risk for early retirement. In total, n = 352 patients will be randomised with a 1:1 allocation to intervention or control group and stratified by primary care practice using permuted blocks. The primary outcome is the number of days of sick leave during a 12-month period after the assumed completion of treatments (t1 to t2). Secondary outcomes include the number of days of sick leave (self-report), work ability, and health-related quality of life, as well as data from the qualitative process evaluation. Discussion: The results of the study will inform the design of future care services and provide valuable information on multidisciplinary case management in the context of rehabilitation care planning. The results of the qualitative process evaluation will further contribute to the understanding of facilitating and hindering factors. Trial registration: DRKS-German Clinical Trials Register, DRKS0 00242 07. Registered on 22 March 2021. [ABSTRACT FROM AUTHOR]

Introduction: Symptomatic hip osteoarthritis (OA) causes significant morbidity and functional limitations. While corticosteroid injections (CSI) are commonly offered and administered for OA pain relief, it is unknown if they offer any clinically meaningful long-term benefit or reduce the overall need for surgical intervention. Methods: A cross-sectional retrospective cohort study was performed on primary hip osteoarthritis patients from a single academic tertiary-care center arthroplasty clinic from 2014 to 2019. Patients were divided into three groups. CSI + THA: hip CSI patients who underwent subsequent ipsilateral THA. CSI-noTHA: hip CSI who have not had ipsilateral THA to date. THA-noCSI: a control group of consecutive hip OA patients who underwent primary THA without prior CSI. Demographic variables, injection relief duration, and radiographic arthritis severity were recorded. Time from clinic presentation to injection and/or THA were compared. Results: 357 patients met inclusion criteria and underwent guided, arthroplasty provider-ordered CSI. Mean duration of relief was 6.7 weeks (SD 8.7). 244 injection patients (67.2%) subsequently underwent THA (CSI + THA). 150 of 390 patients have not undergone THA at mean of 25.5 months follow-up. Mean time from clinic presentation to THA was 8.6 months longer after CSI (16.3, SD 17.8) months in CSI patients compared to 7.7 (SD 10.6) months for patients without CSI (p < 0.001). Of 117 patients in the CSI-noTHA group at mean 25 months follow-up, only 43 (12% of all injection patients) had not had THA because they found injections effective. The remaining 74 (63%) of CSI-noTHA patients have been deemed medically unfit for surgery or are currently scheduled for THA. Discussion/Conclusion: The results of this study suggest the utilization of intra-articular CSI as conservative treatment in an arthroplasty clinic does not prolong time to THA for a clinically important duration. The use of CSI should be reserved for diagnostic purposes and/or short-term pain relief in poor surgical candidates. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Background: Traditional medical research infrastructures relying on the Centers of Excellence (CoE) model (an infrastructure or shared facility providing high standards of research excellence and resources to advance scientific knowledge) are often limited by geographic reach regarding patient accessibility, presenting challenges for study recruitment and accrual. Thus, the development of novel, patient-centered (PC) strategies (e.g., the use of online technologies) to support recruitment and streamline study procedures are necessary. This research focused on an implementation evaluation of a design innovation with implementation outcomes as communicated by study staff and patients for CoE and PC approaches for a randomized controlled trial (RCT) for patients with vasculitis. Methods: In-depth qualitative interviews were conducted with 32 individuals (17 study team members, 15 patients). Transcripts were coded using the Consolidated Framework for Implementation Research (CFIR). Results: The following CFIR elements emerged: characteristics of the intervention, inner setting, characteristics of individuals, and process. From the staff perspective, the communication of the PC approach was a major challenge, but should have been used as an opportunity to identify one "point person" in charge of all communicative elements among the study team. Study staff from both arms were highly supportive of the PC approach and saw its promise, particularly regarding online consent procedures. Patients reported high self-efficacy in reference to the PC approach and utilization of online technologies. Local physicians were integral for making patients feel comfortable about participation in research studies. Conclusions: The complexity of replicating the interpersonal nature of the CoE model in the virtual setting is substantial, meaning the PC approach should be viewed as a hybrid strategy that integrates online and face-to-face practices. Trial registrations: 1) Name: The Assessment of Prednisone In Remission Trial – Centers of Excellence Approach (TAPIR). Trial registration number: ClinicalTrials.gov NCT01940094. Date of registration: September 10, 2013. 2) Name: The Assessment of Prednisone In Remission Trial – Patient Centric Approach (TAPIR). Trial registration number: Clinical Trials.gov NCT01933724. Date of registration: September 2, 2013. [ABSTRACT FROM AUTHOR]

Accurate prostate cancer (PCa) patient diagnosis and risk assessment are key to ensure the best outcome. Currently, low- and favorable intermediate-risk PCa patients may be offered AS due to the indolent nature of the disease. Nonetheless, deciding between active surveillance and curative-intent treatment remains an intricate task, as a subset of these patients may eventually progress, enduring poorer prognosis. Herein, we sought to construct risk calculators based on cancer biomarkers, enabling more accurate discrimination among patients which may benefit from active interventions. Ki67 immunoscore, GSTP1 and KLF8 promoter methylation levels (me) were assessed in PCa tissues. Study endpoints included overall and biochemical recurrence-free (BCR) survival. Combination with relevant clinicopathological parameters allowed for construction of graphical calculating tools (nomograms). Higher Ki67 index correlated with worse BCR-free survival, whereas higher KLF8me levels were associated with improved overall survival, especially in patients with lower-grade tumors. GSTP1me levels had no prognostic value. Among prognostic models tested, a BCR-risk calculator – ProstARK (including Ki67 and clinicopathologic parameters) – disclosed 79.17% specificity, 66.67% sensitivity, 55% positive predictive value, 86% negative predictive value, and 75.76% accuracy. Similar results were found using an independent PCa biopsy cohort, validating its prognostication ability. Combining clinicopathologic features and Ki67 index into a risk calculator enables easy and accurate implementation of a novel PCa prognostication tool. This nomogram may be useful for a more accurate selection of patients for active surveillance protocols. Nonetheless, validation in a larger, multicentric, set of diagnostic PCa biopsies is mandatory for further confirmation of these results. [ABSTRACT FROM AUTHOR]

Background: To investigate whether radiomics models derived from pretreatment CT could help to predict response to immunotherapy in oral squamous cell carcinoma (OSCC). Methods: Retrospectively, a total of 40 patients with measurable OSCC were included. The patients were divided into responder group and non-responder group according to the comparison of pre-treatment and post-treatment CT findings. Radiomics features were extracted from pre-treatment CT images, and optimal features were selected by univariate analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis. Neural network, support vector machine, random forest and logistic regression models were used to predict response to immunotherapy in OSCC, and leave-one-out cross validation was employed to assess the performance of the classifiers. The area under the curve (AUC), accuracy, sensitivity and specificity were calculated to quantify the predictive efficacy. Results: A total of 7 features were selected to build models upon machine learning methods. By comparing different machine learning based models, the neural network model achieved the best predictive ability, with an AUC of 0.864, an accuracy of 82.5%, a sensitivity of 82.5%, and a specificity of 82.5%. Conclusions: The pretreatment CT-based radiomics model showed good performance in predicting response to immunotherapy in OSCC. Pretreatment CT-based radiomics model might provide an alternative approach for the selection of patients who benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Background: To ensure high-quality pediatric palliative care (PPC) and enable healthcare professionals (HCPs) to provide person-centered care for the individual child with a life-limiting or life-threatening illness and their family, the Individual Care Plan (ICP) for PPC was developed. However, in practice, the ICP for PPC is not used for all children in need of PPC. Insight into why, for which problem and for which children HCPs wish to use an ICP in PPC is therefore necessary to assure that the ICP can be fully implemented in practice. Methods: Two semi-structured focus group interviews were held with 15 experienced healthcare professionals in PPC. Data were thematically analyzed. Results: Participants wish to use an ICP to collaboratively establish a plan with parents for the current and future care and treatment of the child. By doing so, they hope to achieve coordination and continuity of care, to achieve shared decision-making, and to support parents and other healthcare professionals in the care of the child. Participants think the ICP could also be used in the care for children with complex chronic conditions. Conclusion: The purposes for which healthcare professionals wish to use an ICP in PPC are broader than the purpose for which the ICP for PPC was developed. Future research should focus on whether the use of an ICP in PPC practice can achieve these purposes. [ABSTRACT FROM AUTHOR]

Background and objective: Total Knee Arthroplasty (TKA) has proven highly effective in improving quality of life for patients with severe knee conditions. Despite advancements, surgical complications such as periprosthetic joint infections (PJIs) pose risks. The potential predictive value of pre- and post-operative inflammatory markers like neutrophil-to-lymphocyte ratio (NLR), D-dimer, and albumin levels on surgical outcomes is garnering attention. There is a growing interest in leveraging these markers to enhance patient selection and outcome prediction in the context of TKA.Focusing on the natural course of these markers, and the incidence of PJIs and to refine perioperative care strategies, improve patient outcomes, and identify high-risk patients for targeted intervention. Methods: The study included 94 patients who underwent total knee arthroplasty (TKA) between 2019 and 2023. Blood tests were conducted before surgery and at 1, 3, 7, and 15 days after surgery to assess various parameters including white blood cell count, neutrophils, lymphocytes, platelets, hemoglobin, C-reactive protein, D-dimers, total protein, albumin, and total cholesterol values and ratios. Results: Following total knee arthroplasty (TKA), key observations in blood markers included a sharp rise in white blood cell (WBC) counts from 5.81 to 10.22 (*10^9/L) on the first day post-surgery, with levels returning close to preoperative values by day-15. Neutrophil counts similarly increased from 3.46 to 8.50 (*10^9/L) on day-1, decreasing to 4.01 by day-15. Hemoglobin levels significantly decreased from 115.70 g/L to 90.62 by day-3 before improving to 100.30 by day-15. C-reactive protein (CRP) levels also saw a significant rise from 6.15 mg/L to a peak of 47.07 on day-3, then reducing to 10.55 by day-15, indicating a response to inflammation. Conclusion: Following total knee arthroplasty (TKA), a significant initial postoperative increase in white blood cell count, neutrophils, and C-reactive protein levels, indicative of an acute inflammatory response, before returning towards baseline values by day 15. Hemoglobin levels displayed a notable dip post-surgery, gradually improving by the study's end. These patterns emphasize the dynamic nature of inflammatory and hematological responses after TKA, highlighting their potential role in predicting surgical outcomes and guiding postoperative care. [ABSTRACT FROM AUTHOR]

Background: Intrauterine devices (IUDs) are one of the most popular methods of contraception, and uterine perforation has been presented among the most significant potential complications of IUD use. The aim of this study is to evaluate the risk factors of uterine perforation when using an IUD. Methods: In this retrospective study, all 164 women who have referred to Al-Zahra hospital in Tabriz- Iran to remove the retained IUD from March 2018 to March 2021, were investigated in two groups. Patients in case group underwent surgery to remove the dislocated device and management of its complications. In control group, the devices were removed using a Novak or ring forceps with or without hysteroscopy with no uterine perforation. Data were analyzed using SPSS software, and P < 0.05 was considered statistically significant. P-Value was obtained for qualitative data via Fisher's exact test and Chi-Squared test and for quantitative data via Mann-Whitney U test and independent T-test. Results: The mean age of patients in the groups with or without uterine perforation was 30.57 and 36.78 years respectively (P = 0.01). The frequency of two or more parities among patients with uterine perforation was higher than other patients (P = 0.13). Ultrasound study before (p = 0.037) and after (p = 0.007) IUD insertion was higher among patients without uterine perforation. The less inexperience of healthcare providers (P = 0.013) and lack of scheduled follow-up visits after the IUD insertion (P < 0.001), are the other important factors affecting the uterine perforation. Abdominal pain was the most common compliant of uterine perforation (P < 0.001) and laparoscopy was the most used surgery to remove the misplaced device. Conclusion: Uterine perforation can be effectively prevented by hiring experienced health care providers and appropriate patient selection. [ABSTRACT FROM AUTHOR]

Background: Diabetes is the most prevalent metabolic disease globally. Correct and effective healthcare management requires up-to-date and accurate information at the local level. This level of information allows managers to determine whether the health system has achieved its desired goals in this area. This study aimed to evaluate the adequacy and quality of care for Type 2 diabetes mellitus (T2DM) patients using the Lot quality assurance sampling (LQAS) technique to provide evidence for decision-making at the local level, prioritizing and allocating resources. Methods: A descriptive-analytical study was conducted in 12 supervision areas (SAs)/health facilities in northwestern Iran involving 240 patients with T2DM in primary health care. The selection of patients and determination of SAs were done randomly using the LQAS technique. Glycated Hemoglobin (HbA1c) was used to evaluate patients' blood sugar control in each SA. Multiple linear regression analysis was used to estimate predictors of HbA1c in T2DM. Results: The overall average of HbA1c value was 7.84%. The HbA1c level was > 7% in 148 (61.6%) of the patients. Among the 12 SAs, the LQAS identified unacceptable quality of care in 5 SAs. In the final analysis, each unit increase in fasting blood sugar (FBS), High-density lipoprotein (HDL), Low-density lipoprotein (LDL), and Thyroglobulin (TG) values resulted in an increased in HbA1c levels by 0.43, 0.183, 0.124, and 0.182 times, respectively. However, with a one-unit increase in the care of a family physician and nutritionist, along with regular physical activity, HbA1c levels decreased by − 0.162, -0.74, and − 0.11 times, respectively. Conclusions: The quality of care for diabetic patients needs improvement in some SAs. Findings indicated that the LQAS technique effectively identifies centers/areas with substandard diabetes care quality and efficiently allocates resources to those in need. It is recommended to implement corrective measures in areas with inadequate care quality. [ABSTRACT FROM AUTHOR]

Background: Risk stratification and treatment benefit prediction models are urgent to improve negative sentinel lymph node (SLN-) melanoma patient selection, thus avoiding costly and toxic treatments in patients at low risk of recurrence. To this end, the application of artificial intelligence (AI) could help clinicians to better calculate the recurrence risk and choose whether to perform adjuvant therapy. Methods: We made use of AI to predict recurrence-free status (RFS) within 2-years from diagnosis in 94 SLN- melanoma patients. In detail, we detected quantitative imaging information from H&E slides of a cohort of 71 SLN- melanoma patients, who registered at Istituto Tumori "Giovanni Paolo II" in Bari, Italy (investigational cohort, IC). For each slide, two expert pathologists firstly annotated two Regions of Interest (ROIs) containing tumor cells alone (TUMOR ROI) or with infiltrating cells (TUMOR + INF ROI). In correspondence of the two kinds of ROIs, two AI-based models were developed to extract information directly from the tiles in which each ROI was automatically divided. This information was then used to predict RFS. Performances of the models were computed according to a 5-fold cross validation scheme. We further validated the prediction power of the two models on an independent external validation cohort of 23 SLN- melanoma patients (validation cohort, VC). Results: The TUMOR ROIs have revealed more informative than the TUMOR + INF ROIs. An Area Under the Curve (AUC) value of 79.1% and 62.3%, a sensitivity value of 81.2% and 76.9%, a specificity value of 70.0% and 43.3%, an accuracy value of 73.2% and 53.4%, were achieved on the TUMOR and TUMOR + INF ROIs extracted for the IC cohort, respectively. An AUC value of 76.5% and 65.2%, a sensitivity value of 66.7% and 41.6%, a specificity value of 70.0% and 55.9%, an accuracy value of 70.0% and 56.5%, were achieved on the TUMOR and TUMOR + INF ROIs extracted for the VC cohort, respectively. Conclusions: Our approach represents a first effort to develop a non-invasive prognostic method to better define the recurrence risk and improve the management of SLN- melanoma patients. [ABSTRACT FROM AUTHOR]

Background: Dads and Daughters Exercising and Empowered (DADEE) is a program targeting fathers/father-figures to improve their daughters' physical activity and well-being. Previous randomised controlled efficacy and effectiveness trials of DADEE demonstrated meaningful improvements in a range of holistic outcomes for both fathers and daughters in the short-term. This study aims to assess the long-term impact (12-months) of the program when delivered in the community by trained facilitators. Methods: Fathers/father-figures and their primary school-aged daughters were recruited from Newcastle, Australia into a single-arm, non-randomised, pre-post study with assessments at baseline, 10-weeks (post-intervention) and 12-months. The 9-session program included weekly 90-min educational and practical sessions, plus home-based tasks. The primary outcome was fathers' and daughters' days per week meeting national physical activity recommendations (≥ 30 min/day of MVPA for fathers, ≥ 60 min/day MVPA for daughters). Secondary outcomes included physical activity, screen time, self-esteem, father-daughter relationship, social-emotional well-being, parenting measures, and process outcomes (including recruitment, attendance, retention and program acceptability). Results: Twelve programs were delivered with 257 fathers (40.0 ± 9.2 years) and 285 daughters (7.7 ± 1.9 years). Mixed effects regression models revealed significant intervention effects for the primary outcome, with fathers increasing the days/week meeting physical activity recommendations by 27% at 10-weeks (p < 0.001) and by 19% at 12-months (p < 0.001) compared with baseline. Likewise, for daughters there was a significant increase by 25% at 10-weeks (p < 0.001) and by 14% at 12-months (p = 0.02) when compared to baseline. After conducting a sensitivity analysis with participants unaffected by COVID-19 lockdowns (n = 175 fathers, n = 192 daughters), the primary outcome results strengthened at both time-points for fathers and at 12-months for daughters. Additionally, the sensitivity analysis revealed significant intervention effects at post-program and 12-months for all secondary outcomes in both fathers and daughters. Furthermore, the process outcomes for recruitment capability, attendance, retention and satisfaction levels were high. Conclusions: Findings provide support for a sustained effect of the DADEE program while delivered in a community setting by trained facilitators. Further investigation is required to identify optimised implementation processes and contextual factors to deliver the program at scale. Trial registration: ACTRN12617001450303. Date registered: 12/10/2017. [ABSTRACT FROM AUTHOR]

Background: Recruitment for neonatal clinical trials can be particularly challenging. Low enrollment rates bias the research population and decrease generalizability of findings. We identified a critical need for an intervention to improve how researchers recruit for neonatal clinical trials. Working within the US neonatal research context, we developed the Better Research Interactions for Every Family (BRIEF) Intervention, which had two overarching goals: to improve the recruitment experience for all parents, focusing on minoritized populations, and to increase participation, focusing on decreasing disparities in research participation. Methods: We used intervention mapping (IM) to guide all steps of intervention development. IM is a planning framework that provides a systematic process and detailed protocol for step-by-step decision-making for intervention development, implementation, and evaluation. Results: We performed IM's six steps. In step 1, we convened two stakeholder groups, a parent panel and an expert panel, who provided guidance through development of all BRIEF components. Through a recent systematic review, empirical data collected by our team, and consultations with the panels, we identified key determinants (barriers and facilitators) of low enrollment rates and research team members as change agents. In step 2, we iteratively refined our list of key factors to include and linked determinants of behavior changes to these performance objectives. In step 3, we chose three theories (social cognitive theory, theory of information processing, and the trans-theoretical model), methods from identified practical applications suitable for the population (research team members) and the context (busy research NICU teams). In step 4, we developed and refined the intervention components, including self-guided pre-work and a single in-person session. In step 5, we identified the Darbepoetin plus slow-release intravenous iron trial as our partner study in which to pilot BRIEF. In step 6, we developed a multi-stage evaluation plan that included five distinct levels of outcomes. Conclusions: This manuscript shares our rationale and processes for the creation of a research team member-facing intervention aiming to improve recruitment processes for neonatal clinical trials. Our approach can inform those aiming to improve recruitment for neonatal clinical trials and those who may be considering use of IM within similar contexts. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of Internet-based self-help interventions in treating depression in adolescents and young adults. Methods: A systematic search was conducted across six databases, including PubMed, to identify randomized controlled trials (RCTs) that satisfied the specified inclusion and exclusion criteria. The intervention measure consisted of Internet-based self-help interventions. Results: A total of 23 randomized controlled trials (RCTs) were included in this analysis. Meta-analysis indicated that Internet-based self-help therapies significantly reduced depression scores in adolescents and young adults. (OR = -0.68, 95%CI [-0.88, -0.47], P < 0.001). We examined the effects of patient recruitment from various regions, medication usage, therapist involvement, weekly intervention time, and intervention duration. Patients selected from school, primary healthcare centers, clinics and local communities had better results. Intervention lasting 30 to 60 min and 60 to180 minutes per week were effective in the short term. Conclusion: The internet-based self-help intervention can be effective in treating depression in adolescents and young adults. However, factors such as patient recruitment locations, medication usage, Therapists' involvement, weekly intervention time, and intervention duration interacted with the outcome. Subgroup analysis on potential adverse effects and gender was impossible due to insufficient data from the included studies. [ABSTRACT FROM AUTHOR]

A study published in Translational Neurodegeneration introduces a new blood-based biomarker, the plasma p-tau181 assay, which accurately reflects tau pathology in Alzheimer's disease (AD). Unlike current assays, this new biomarker is not affected by amyloid accumulation and shows higher specificity for tau pathology. It has the potential to detect and stage AD tau pathologies in the brain, offering a more accessible and functional alternative to PET scans. The assay may also help predict therapeutic response to current treatments and identify suitable patients for anti-amyloid therapies. However, more research with larger sample sizes is needed to confirm these findings. [Extracted from the article]

Objectives: Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group. Methods: A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS). Results: A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified. Conclusions: The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach. [ABSTRACT FROM AUTHOR]

Monetary incentives are commonly used to help recruit trial participants. Some studies have found greater recruitment with larger incentives, while others have found smaller incentives more cost-effective in terms of cost per participant. As part of an implementation study, we compared the impact of four approaches to recruitment, three of which involved phone recruitment with varying financial incentives. Adding modest financial incentives reliably increased the recruitment ratio, and greater incentives increased recruitment more than smaller incentives. However, recruiters required less time to obtain agreement to participate when the greater incentive was offered, and these time savings made the greater incentive cost-saving relative to the smaller incentive and cost-effective relative to no incentive. Our results suggest the possibility of a "sweet spot" for financial incentives, and that trial designers should consider pilot-testing incentive levels in the context of their other recruitment costs to determine whether paying participants more may be cost-saving for trial sponsors. [ABSTRACT FROM AUTHOR]

Background: Opioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We assessed the feasibility of implementing a Take-home Naloxone (THN) intervention in emergency settings, as part of designing a definitive randomised controlled trial (RCT). Methods: We undertook a clustered RCT on sites pairing UK Emergency Departments (ED) and ambulance services. At intervention sites, we recruited emergency healthcare practitioners to supply THN to patients presenting with opioid overdose or related condition, with recruitment across 2019–2021. We assessed feasibility of intervention implementation against four predetermined progression criteria covering site sign up and staff training; identification of eligible patients; issue of THN kits and Serious Adverse Events. Results: At two intervention sites, randomly selected from 4, 299/687 (43.5%) clinical staff were trained (ED1 = 107, AS1 = 121, ED2 = 25, AS2 = 46). Sixty THN kits were supplied to eligible patients (21.7%) (n: ED1 = 36, AS1 = 4, ED2 = 16, AS2 = 4). Across sites, kits were not issued to eligible patients on a further 164 occasions, with reasons reported including: staff forgot (n = 136), staff too busy (n = 15), and suspected intentional overdose (n = 3), no kit available (n = 2), already given by drugs nurse (n = 4), other (n = 4). Staff recorded 626 other patients as ineligible but considered for inclusion, with reasons listed as: patient admitted to hospital (n = 194), patient absconded (n = 161) already recruited (n = 64), uncooperative or abusive (n = 55), staff not trained (n = 43), reduced consciousness level (n = 41), lack of capacity (n = 35), patient in custody (n = 21), other (n = 12). No adverse events were reported. Conclusion: Staff and patient recruitment were low and varied widely by site. This feasibility study did not meet progression criteria; a fully powered RCT is not planned. Trial Registration: ISRCTN13232859 (Registered 16/02/2018). [ABSTRACT FROM AUTHOR]

Background: Healing Right Way (HRW) aimed to improve health outcomes for Aboriginal Australians with stroke or traumatic brain injury by facilitating system-level access to culturally secure rehabilitation services. Using a stepped-wedge randomised controlled trial (RCT) design (ACTRN12618000139279, 30/01/2018), a two-pronged intervention was introduced in four rural and four urban hospitals, comprising 1.Cultural security training (CST) for staff and 2.Training/employment of Aboriginal Brain Injury Coordinators (ABIC) to support Aboriginal patients for 6-months post-injury. Three-quarters of recruited patients lived rurally. The main outcome measure was quality-of-life, with secondary outcomes including functional measures, minimum processes of care (MPC); number rehabilitation occasions of service received, and improved hospital experience. Assessments were undertaken at baseline, 12- and 26-weeks post-injury. Only MPCs and hospital experience were found to improve among intervention patients. We report on the process evaluation aiming to support interpretation and translation of results. Methods: Using mixed methods, the evaluation design was informed by the Consolidated Framework for Implementation Research. Data sources included minutes, project logs, surveys, semi-structured interviews, and observations. Four evaluation questions provided a basis for systematic determination of the quality of the trial. Findings from separate sources were combined to synthesise the emerging themes that addressed the evaluation questions. Three components were considered separately: the trial process, CST and ABIC. Results: The complex HRW trial was implemented to a satisfactory level despite challenging setting factors, particularly rural–urban system dynamics. Patient recruitment constraints could not be overcome. The vulnerability of stepped-wedge designs to time effects influenced recruitment and trial results, due to COVID. Despite relatively high follow-up, including to rural/remote areas, data points were reduced. The lack of culturally appropriate assessment tools influenced the quality/completeness of assessment data. The ABIC role was deemed feasible and well-received. The CST involved complex logistics, but rated highly although online components were often incomplete. Project management was responsive to staff, patients and setting factors. Conclusions: Despite mostly equivocal results, the ABIC role was feasible within mainstream hospitals and the CST was highly valued. Learnings will help build robust state-wide models of culturally secure rehabilitation for Aboriginal people after brain injury, including MPC, workforce, training and follow-up. [ABSTRACT FROM AUTHOR]

Background: The number of surgical trials is increasing but such trials can be complex to deliver and pose specific challenges. A multi-centre, Phase III, RCT comparing Posterior Cervical Foraminotomy versus Anterior Cervical Discectomy and Fusion in the Treatment of Cervical Brachialgia (FORVAD Trial) was unable to recruit to target. A rapid qualitative study was conducted during trial closedown to understand the experiences of healthcare professionals who participated in the FORVAD Trial, with the aim of informing future research in this area. Methods: Semi-structured interviews were conducted with 18 healthcare professionals who had participated in the FORVAD Trial. Interviews explored participants' experiences of the FORVAD trial. A rapid qualitative analysis was conducted, informed by Normalisation Process Theory. Results: Four main themes were generated in the data analysis: (1) individual vs. community equipoise; (2) trial set-up and delivery; (3) identifying and approaching patients; and (4) timing of randomisation. The objectives of the FORVAD trial made sense to participants and they supported the idea that there was clinical or collective equipoise regarding the two FORVAD interventions; however, many surgeons had treatment preferences and lacked individual equipoise. The site which had most recruitment success had adopted a more structured process for identification and recruitment of patients, whereas other sites that adopted more "ad hoc" screening strategies struggled to identify patients. Randomisation on the day of surgery caused both medico-legal and practical concerns at some sites. Conclusions: Organisation and implementation of a surgical trial in neurosurgery is complex and presents many challenges. Sites often reported low recruitment and discussed the logistical issues of conducting a complex surgical RCT. Future trials in neurosurgery may need to offer more flexibility and time during set-up to maximise opportunities for larger recruitment numbers. Rapid qualitative analysis informed by Normalisation Process Theory was able to quickly identify key issues with trial implementation so rapid qualitative analysis may be a useful approach for teams conducting qualitative research in trials. Trial registration: ISRCTN, ISRCTN reference: 10,133,661. Registered 23rd November 2018. [ABSTRACT FROM AUTHOR]

Background: Lack of diversity in participants throughout the research process limits the generalizability of findings and may contribute to health disparities. There are unique challenges to recruitment of families to pediatric cancer research studies, especially for those from disadvantaged backgrounds. Thus, there is a need to evaluate the most effective recruitment and retention strategies to optimize equitable recruitment of diverse participants. Methods: The present study adapted and implemented methods outlined previously in the literature. These previous efforts were developed to address barriers to pediatric research, behavioral health intervention research and research with Black adolescents. Recruitment and retention strategies are described across four different time points: pre-approach, initial connection, building connection and follow-up. Eligible families of children with a pediatric cancer diagnosis were approached during a routine oncology visit. Once consented, enrollment and retention rates over three timepoints of data collection were recorded and evaluated. Results: Results indicated high rates of enrollment (86%) and retention (95%) for eligible participants. There were no trends in heightened attrition for any specific subgroup. Conclusions: The findings of this study are promising and suggest these recruitment and retention strategies may be useful in recruiting individuals from disadvantaged backgrounds. [ABSTRACT FROM AUTHOR]

Background: Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. Methods: The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. Results: 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p < 0.05). High-order aberrations decreased significantly (p < 0.05). Despite the high incidence of posterior capsule opacification (83.2%), managed with early Nd: YAG capsulotomy, no other severe complications were reported. Patient-reported outcomes indicated high satisfaction, with an average VF-14 score of 94.3 ± 10.2 and 93.5% achieving complete spectacle independence. Halo (66.2%) was the most commonly reported optical phenomena, followed by glare (18.2%), and starburst (7.8%) after surgery. Conclusions: Bilateral RLE with trifocal IOLs in presbyopic patients without cataracts significantly improves visual acuity and reduces ocular aberrations in presbyopic patients. The procedure offers high patient satisfaction and spectacle independence, though it requires careful patient selection and management of expectations regarding potential photic phenomena. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a serious public health problem affecting 37.3 million Americans. Diabetes shared medical appointments (SMAs) are an effective strategy for providing diabetes self-management support and education in primary care. However, practices delivering SMAs experience implementation challenges. This analysis examined conditions associated with successful practice implementation of diabetes SMAs in the context of participation in a pragmatic trial. Methods: Mixed methods study using qualitative and quantitative data collected from interviews, observations, surveys, and practice-reported data, guided by the practical, robust implementation and sustainability model (PRISM). Data were analyzed using qualitative comparative analysis (QCA). Successful implementation was defined as meeting patient recruitment targets (Reach) during the study period. Participants were clinicians and staff members from 22 primary care practices in Colorado and Missouri, USA. Results: The first necessary condition identified from the QCA was the presence of additional resources for patients with diabetes in the practice. Within practices that had these additional resources, we found that a sufficiency condition was the presence of an effective key person to make things happen with the SMAs. A second QCA was conducted to determine conditions underlying the presence of the effective key person (often performing functions of an implementation champion), which revealed factors including low or managed employee turnover, a strong baseline practice culture, and previous experience delivering SMAs. Conclusions: Identification of key factors necessary and sufficient for implementation of new care processes is important to enhance patient access to evidence-based interventions. This study suggests that practice features and resources have important implications for implementation of diabetes SMAs. There may be opportunities to support practices with SMA implementation by enabling the presence of skilled implementation champions. Trial registration: Registered at clinicaltrials.gov under trial ID NCT03590041, registered on July 18, 2018. [ABSTRACT FROM AUTHOR]

Background: Dental caries is a global public health concern, and early detection is essential. Traditional methods, particularly visual examination, face access and cost challenges. Teledentistry, as an emerging technology, offers the possibility to overcome such barriers, and it must be given high priority for assessment to optimize the performance of oral healthcare systems. The aim of this study was to systematically review the literature evaluating the diagnostic accuracy of teledentistry using photographs taken by Digital Single Lens Reflex (DSLR) and smartphone cameras against visual clinical examination in either primary or permanent dentition. Methods: The review followed PRISMA-DTA guidelines, and the PubMed, Scopus, and Embase databases were searched through December 2022. Original in-vivo studies comparing dental caries diagnosis via images taken by DSLR or smartphone cameras with clinical examination were included. The QUADAS-2 was used to assess the risk of bias and concerns regarding applicability. Meta-analysis was not performed due to heterogeneity among the studies. Therefore, the data were analyzed narratively by the research team. Results: In the 19 studies included, the sensitivity and specificity ranged from 48 to 98.3% and from 83 to 100%, respectively. The variability in performance was attributed to factors such as study design and diagnostic criteria. Specific tooth surfaces and lesion stages must be considered when interpreting outcomes. Using smartphones for dental photography was common due to the convenience and accessibility of these devices. The employment of mid-level dental providers for remote screening yielded comparable results to those of dentists. Potential bias in patient selection was indicated, suggesting a need for improvements in study design. Conclusion: The diagnostic accuracy of teledentistry for caries detection is comparable to that of traditional clinical examination. The findings establish teledentistry's effectiveness, particularly in lower income settings or areas with access problems. While the results of this review is promising, conducting several more rigorous studies with well-designed methodologies can fully validate the diagnostic accuracy of teledentistry for dental caries to make oral health care provision more efficient and equitable. Registration: This study was registered with PROSPERO (CRD42023417437). [ABSTRACT FROM AUTHOR]

Background: Recruitment for clinical trials and large-scale studies is challenging, especially for patients with complex conditions like chronic pain. Email recruitment has the potential to increase efficiency, to reduce costs, and to improve access for underrepresented patient populations. The objective of this study was to examine the effectiveness, efficiency, and equitability of email versus postal mail recruitment for the Learning to Apply Mindfulness to Pain (LAMP) study, a three-site clinical trial of mindfulness-based interventions for chronic pain. Methods: Patients with chronic pain diagnoses were recruited from three United States Department of Veterans Affairs (VA) facilities using the VA electronic health record (EHR). Recruitment materials were sent using either postal mail (n = 7986) or email (n = 19,333). Patients in the email recruitment group were also mailed introductory postcards before any emails. Mailing addresses and email addresses were obtained from the EHR. Effectiveness was measured by the response rate of patients who logged into the secure LAMP study website. Efficiency was measured by the number of days from when the recruitment materials were sent to when patients logged into the LAMP portal as well as the estimated costs of each recruitment approach. To assess equitability, we examined whether email recruitment was less effective for underrepresented populations, based on demographic information from the EHR. Results: Effectiveness—unadjusted response rates were greater for email versus postal-mail recruitment (18.9% versus 6.3%), and adjusted response rates were over three times greater for email recruitment (RR = 3.5, 95% CI 3.1–3.8) based on a multivariable analysis controlling for age, gender, race, ethnicity, rurality, and site. Efficiency—email recruitment had a significantly lower mean response time (1 day versus 8 days) and a lower cost. Equity—email recruitment led to higher response rates for all subpopulations, including older, non-White, Hispanic, rural, and female Veterans. Conclusions: Email recruitment is an effective, efficient, and equitable way to recruit VA patients to large-scale, chronic pain clinical trials. Trial registration: Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020. [ABSTRACT FROM AUTHOR]

Background: Endovascular treatment (ET) options for acute stroke due to distal middle cerebral artery occlusions are rapidly evolving, but data on outcome and safety are sparse. We therefore performed an analysis of patients undergoing ET for primary M3 occlusions in routine clinical practice in a nationwide registry. Methods: Patients enrolled between 01/20 and 12/21 in the prospective, multicenter German Stroke Registry-Endovascular Treatment (GSR-ET) were screened for mechanical thrombectomy performed for primary M3 occlusion. We analyzed neurological deficit as measured by the National Institute of Health Stroke Scale (NIHSS), symptomatic intracranial hemorrhage (sICH), thrombectomy technique, successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3) and functional outcome as measured by the modified Rankin Scale (mRS) at discharge and 90 days. Results: Out of 5574 patients, 11 patients (0.2%, median age 80 years, 54.5% female) underwent ET for primary M3 occlusion. All patients had pre-admission mRS ≤ 1, median NIHSS on admission was 8, and successful reperfusion was achieved in 6/11 patients (54.5%). While no vasospasm, dissection or perforation was reported, symptomatic intracranial hemorrhage occurred in 2 patients (18.2%). Favorable outcome (mRS ≤ 2) was achieved in 6/11 patients (54.5%) at 90-day follow-up. Conclusions: ET for primary M3 occlusions is rarely performed. While technically feasible, the procedure's potential benefits must be carefully weighed against its associated risks, including clinically relevant complications. Caution and further research is needed to optimize patient selection for this intervention. Trial Registration: GSR-ET; ClinicalTrials.gov Identifier: NCT03356392; Trial Registration Date: 11/29/2017. [ABSTRACT FROM AUTHOR]

Objective: To assess first-trimester recruitment and retention of pregnant patients who regularly used cannabis, but not other substances, measured by willingness to participate in a research study, completion of self-administered electronic questionnaires, and willingness to provide urine samples during each trimester of pregnancy. We designed and launched a prospective feasibility study titled, Cannabis Legalization in Michigan (CALM) – Maternal & Infant Health (MIH), in two Michigan clinics after the recreational use of cannabis became legal for adults 21 years and older. Results: Over half (52%) of patients asked to participate in CALM-MIH were consented to the study. Two-thirds (66%) of screened patients initiated prenatal care during their first trimester of pregnancy and 50% used cannabis, of which the majority did not concurrently use other substances. Of those recruited into the prospective study, all participants completed the first-trimester questionnaire and provided urine samples. Study retention was 80% and all participants who completed follow-up assessments were willing to provide urine samples. [ABSTRACT FROM AUTHOR]

The COTAT (Collaborative Opioid Taper After Trauma) Study was a randomized trial of an opioid taper support program using a physician assistant (PA) to provide pain and opioid treatment guidance to primary care providers assuming care for adult patients with moderate to severe trauma discharged from a Level I trauma center on opioid therapy. Patients were recruited, assessed, and randomized individually by a surgery research recruitment team one to two days prior to discharge to home. Participants randomized to the opioid taper support program were contacted by phone within a few days of discharge by the PA interventionist to confirm enrollment and their primary care provider (PCP). The intervention consisted of PA support as needed to the PCP concerning pain and opioid care at weeks 1, 2, 4, 8, 12, 16, and 20 after discharge or until the PCP office indicated they no longer needed support or the patient had tapered off opioids. The PA was supervised by a pain physician-psychiatrist, a family physician, and a trauma surgeon. Patients randomized to usual care received standard hospital discharge instructions and written information on managing opioid medications after discharge. Trial results were analyzed using repeated measures analysis. 37 participants were randomized to the intervention and 36 were randomized to usual care. The primary outcomes of the trial were pain, enjoyment, general activity (PEG score) and mean daily opioid dose at 3 and 6 months after hospital discharge. Treatment was unblinded but assessment was blinded. No significant differences in PEG or opioid outcomes were noted at either time point. Physical function at 3 and 6 months and pain interference at 6 months were significantly better in the usual care group. No significant harms of the intervention were noted. COVID-19 (corona virus 2019) limited recruitment of high-risk opioid tolerant subjects, and limited contact between the PA interventionist and the participants and the PCPs. Our opioid taper support program failed to improve opioid and pain outcomes, since both control and intervention groups tapered opioids and improved PEG scores after discharge. Future trials of post-trauma opioid taper support with populations at higher risk of persistent opioid use are needed. This trial is registered at clinicaltrials.gov under NCT04275258 19/02/2020. This trial was funded by a grant from the Centers for Disease Control and Prevention to the University of Washington Harborview Injury Prevention & Research Center (R49 CE003087, PI: Monica S. Vavilala, MD). The funder had no role in the analysis or interpretation of the data. [ABSTRACT FROM AUTHOR]

Multi-omics sequencing is poised to revolutionize clinical care in the coming decade. However, there is a lack of effective and interpretable genome-wide modeling methods for the rational selection of patients for personalized interventions. To address this, we present iGenSig-Rx, an integral genomic signature-based approach, as a transparent tool for modeling therapeutic response using clinical trial datasets. This method adeptly addresses challenges related to cross-dataset modeling by capitalizing on high-dimensional redundant genomic features, analogous to reinforcing building pillars with redundant steel rods. Moreover, it integrates adaptive penalization of feature redundancy on a per-sample basis to prevent score flattening and mitigate overfitting. We then developed a purpose-built R package to implement this method for modeling clinical trial datasets. When applied to genomic datasets for HER2 targeted therapies, iGenSig-Rx model demonstrates consistent and reliable predictive power across four independent clinical trials. More importantly, the iGenSig-Rx model offers the level of transparency much needed for clinical application, allowing for clear explanations as to how the predictions are produced, how the features contribute to the prediction, and what are the key underlying pathways. We anticipate that iGenSig-Rx, as an interpretable class of multi-omics modeling methods, will find broad applications in big-data based precision oncology. The R package is available: https://github.com/wangxlab/iGenSig-Rx. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive lung disease (COPD) has diverse molecular pathomechanisms and clinical courses which, however, are not fully mirrored by current therapy. Intermittent hypoxemia is a driver of lung function decline and poor outcome, e.g., in patients with concomitant obstructive sleep apnea. Transient hypoxemia during physical exercise has been suggested to act in a similar manner. The PROSA study is designed to prospectively assess whether the clinical course of COPD patients with or without exertional desaturation differs, and to address potential pathophysiological mechanisms and biomarkers. Methods: 148 COPD patients (GOLD stage 2–3, groups B or C) will undergo exercise testing with continuous pulse oximetry. They will be followed for 36 months by spirometry, echocardiography, endothelial function testing, and biomarker analyses. Exercise testing will be performed by comparing the 6-min walk test (6MWT), bicycle ergometry, and a 15-sec breath-hold test. Exertional desaturation will be defined as SpO2 < 90% or delta-SpO2 ≥ 4% during the 6MWT. The primary endpoint will be the rate of decline of FEV1(LLN) between COPD patients with and without exertional desaturation. Discussion: The PROSA Study is an investigator-initiated prospective study that was designed to prove or dismiss the hypothesis that COPD patients with exertional desaturation have a significantly more rapid rate of decline of lung function as compared to non-desaturators. A 20% difference in the primary endpoint was considered clinically significant; it can be detected with a power of 90%. If the primary endpoint will be met, exercise testing with continuous pulse oximetry can be used as a ubiquitously available, easy screening tool to prospectively assess the risk of rapid lung function decline in COPD patients at an early disease stage. This will allow to introduce personalized, risk-adapted therapy to improve COPD outcome in the long run. PROSA is exclusively funded by public funds provided by the European Research Council through an ERC Advanced Grant. Patient recruitment is ongoing; the PROSA results are expected to be available in 2028. Trial registration: The PROSA Study has been prospectively registered at clinicaltrials.gov (register no. NCT06265623, dated 09.02.2024). [ABSTRACT FROM AUTHOR]

Background: To overcome of patients with COVID-19 over the capacity of hospitals and mild to moderate severity of the disease in most cases, the World Health Organization and the Centers for Disease Control and Prevention in the United States, recommend home care for these patients. Receiving care at home will face challenges that can be context-based, especially in crises like the Coronavirus pandemic. The present study aimed to describe the experiences of patients with COVID-19 and their relatives from receiving professional home care nursing. Methods: This study was conducted using a qualitative content analysis method. Nine participants with COVID-19 who were receiving home care nursing in Semnan participated in this study. The purposive sampling method was used. Sampling continued until no new categories appeared, meaning the category's theoretical saturation. Deep and semi-structured interviews were used to collect data based on the research question. Data was analyzed using the conventional content analysis method using Graneheim and Lundman's approach. Results: After analyzing the interviews and comparing codes based on similarities and differences, three main themes, 11 categories, and 30 subcategories were identified. The main themes included "The value of home care" (personalization of care, being economical, providing intellectual security, and reducing the concern of family), "Comprehensive care" (professional commitment, empathy, mastery in care, and patronage), and "Care challenges" (cultural barriers, inadequate services, and lack of information about costs and conditions). Conclusion: The patients with COVID-19 who received professional nursing care at home mentioned some challenges, such as the caregiver not being of the same sex as the patient, delay in receiving the service, the inadequacy of the centers, the limitation of the right to choose the care provider, and insufficient information about the cost of services received before receiving each care. [ABSTRACT FROM AUTHOR]

Purpose: Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric measurements for prognostication at first tumour recurrence. Methods: We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery. Results: Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI [1.18, 5.57]; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI [0.95, 0.99]; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI [0.19, 0.98]; p = 0.04) were shown to have a better survival. Conclusion: Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis. [ABSTRACT FROM AUTHOR]

The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have ensured the correct selection of patients on these trials, supported target engagement and have been used to support claims of disease modification and clinical efficacy. Ultimately, this has recently led to approval of disease-modifying, amyloid-targeting therapies for AD; something that should be noted for clinical trials investigating tau-targeting therapies for AD. There is a clear overlap of the purpose of biomarker use at each stage of clinical development between amyloid-targeting and tau-targeting clinical trials. However, there are differences within the potential context of use and interpretation for some biomarkers in particular measurements of amyloid and utility of soluble, phosphorylated tau biomarkers. Given the complexities of tau in health and disease, it is paramount that therapies target disease-relevant tau and, in parallel, appropriate assays of target engagement are developed. Tau positron emission tomography, fluid biomarkers reflecting tau pathology and downstream measures of neurodegeneration will be important both for participant recruitment and for monitoring disease-modification in tau-targeting clinical trials. Bespoke design of biomarker strategies and interpretations for different modalities and tau-based targets should also be considered. [ABSTRACT FROM AUTHOR]

Background: "Disulfide death," a form of cellular demise, is triggered by the abnormal accumulation of intracellular disulfides under conditions of glucose deprivation. However, its role in the prognosis of glioma remains undetermined. Therefore, the main objective of this study is to establish prognostic signature based on disulfide death-related genes (DDRGs) and to provide new solutions in choosing the effective treatment of glioma. Methods: The RNA transcriptome, clinical information, and mutation data of glioma samples were sourced from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), while normal samples were obtained from the Genotype-Tissue Expression (GTEx). DDRGs were compiled from previous studies and selected through differential analysis and univariate Cox regression analysis. The molecular subtypes were determined through consensus clustering analysis. Further, LASSO analysis was employed to select characteristic genes, and subsequently, a risk model comprising seven DDRGs was constructed based on multivariable Cox analysis. Kaplan-Meier survival curves were employed to assess survival differences between high and low-risk groups. Additionally, functional analyses (GO, KEGG, GSEA) were conducted to explore the potential biological functions and signaling pathways of genes associated with the model. The study also explored immune checkpoint (ICP) genes, immune cell infiltration levels, and immune stromal scores. Finally, the effect of Importin-4(IPO4) on glioma has been further confirmed through RT-qPCR, Western blot, and cell functional experiments. Results: 7 genes associated with disulfide death were obtained and two subgroups of patients with different prognosis and clinical characteristics were identified. Risk signature was subsequently developed and proved to serve as an prognostic predictor. Notably, the high-risk group exhibited an immunosuppressive microenvironment characterized by a high concentration of M2 macrophages and regulatory T cells (Tregs). In contrast, the low-risk group showed lower half-maximal inhibitory concentration (IC50) values. Therefore, patients in the high-risk group may benefit more from immunotherapy, while patients in the low-risk group may benefit more from chemotherapy. In addition, in vitro experiments have shown that inhibition of the expression of IPO4 leads to a significant reduction in the proliferation, migration, and invasion of glioma cells. Conclusion: This study identified two glioma subtypes and constructed a prognostic signature based on DDRGs. The signature has the potential to optimize the selection of patients for immune- and chemotherapy and provided a potential therapeutic target for glioma. [ABSTRACT FROM AUTHOR]

Background: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. Methods and design: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. Discussion: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. Trial registration: ANZCTR ACTRN12622000083796. Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy. Methods: Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response. A novel LM-related signature (LM.SIG) was formulated through an extensive examination of 40 pan-cancer scRNA-seq cohorts. Then, multiple machine learning (ML) algorithms were employed to validate the capacity of LM.SIG for immunotherapy response prediction and survival prognostication based on 8 immunotherapy transcriptomic cohorts and 30 The Cancer Genome Atlas (TCGA) pan-cancer datasets. Moreover, potential targets for immunotherapy were identified based on 17 CRISPR datasets and validated via in vivo and in vitro experiments. Results: The assessment of LM was confirmed to possess a substantial relationship with immunotherapy resistance in 2 immunotherapy scRNA-seq cohorts. Based on large-scale pan-cancer data, there exists a notably adverse correlation between LM.SIG and anti-tumor immunity as well as imbalance infiltration of immune cells, whereas a positive association was observed between LM.SIG and pro-tumorigenic signaling. Utilizing this signature, the ML model predicted immunotherapy response and prognosis with an AUC of 0.73/0.80 in validation sets and 0.70/0.87 in testing sets respectively. Notably, LM.SIG exhibited superior predictive performance across various cancers compared to published signatures. Subsequently, CRISPR screening identified LDHA as a pan-cancer biomarker for estimating immunotherapy response and survival probability which was further validated using immunohistochemistry (IHC) and spatial transcriptomics (ST) datasets. Furthermore, experiments demonstrated that LDHA deficiency in pancreatic cancer elevated the CD8+ T cell antitumor immunity and improved macrophage antitumoral polarization, which in turn enhanced the efficacy of immunotherapy. Conclusions: We unveiled the tight correlation between LM and resistance to immunotherapy and further established the pan-cancer LM.SIG, holds the potential to emerge as a competitive instrument for the selection of patients suitable for immunotherapy. [ABSTRACT FROM AUTHOR]